It is important to detect/measure one or more particular hormones in serum, for a variety of reasons, such as, for example, forassisting in diagnosing the occurrence of an endocrinological disorder, for monitoring the amount of hormones required in hormonal replacement therapy, or for assessing ovulation, pregnancy, contraception, menopause or sexual dysfunction of an individual. Historically, blood collection was required to gather information on the physiological properties of the body, including monitoring women's reproductive cycle. Blood collection is an invasive technique requiring arterial or venous puncture. A patient has to endure discomfort associated with needles or other devices to obtain blood samples for testing. In addition, blood collection sometimes can be associated with problems in various ethnic settings. Therefore, assays of serum hormones are preferably avoided or replaced by alternative non-invasive assays.
In the last decade, considerable attention was paid to substitute assays of serum analytes of interest with assays of urinary analytes of interest. For example, a number of patents and patent applications disclose non-invasive home use fertility tests based on urine analysis (see, for example, U.S. Pat. No. 6,399,398; EP0236023A2; EP0656118B1; EP0703454B1; EP0745853B1; EP0745854B1; EP0728310B1). Those fertility tests are largely based on a series of concentration measurements of urinary estradiol metabolites (e.g., estrone-3-glucuronide, estradiol-3-glucuronide, estradiol-17-glucuronide, estriol-3-glucuronide, estriol-16-glucuronide), urinary luteinising hormone (LH), and/or urinary pregnanediol-3-glucuronide (P3G) (i.e., a progesterone metabolite). To be useful, such concentration data must be determined accurately, usually from a series of samples. For example, a sample may need to be collected daily over an extended sequence of days, and successive daily analyte concentrations are compared to identify a significant concentration change indicative of a change in fertility (ie. fecundity) status. However, there is a natural variation in body fluid source concentration (i.e., “biological concentration variability”) that can interfere with the comparability of such urinary concentration data. The sample to be assayed is collected while urine is being excreted. When the collected sample is analyzed for the presence of a specific analyte, such as an estradiol metabolite, the apparent concentration of the analyte may not be a true reflection of the amount of analyte being produced by the body at that time (i.e., may not be correlated with the serum concentration of the analyte under analysis). The degree of fluid intake, and kidney function, has a very significant influence on the actual volume and frequency of urine excretion and consequently the concentration of the analyte. If fluid intake has been relatively high, or relatively low, during the previous few hours, the measurable concentration of analyte in the collected sample can be much lower (or higher) than normal, leading to inaccurate and possibly misleading information. Additionally, diurnal hormone variations are affected by aging, sleep loss, night or shift work, physical exercise, jet lag, affective disorders and endocrine diseases.
Therefore, there is a need for a non-invasive method of assaying an analyte of relevance to fertility in an alternative body fluid in a constant and more accurate manner.